The hypotheses of this proposal are focused on the molecular and cellular level deficits in genetic models of PKD. The epithelia of the renal tubule are thought to be the primary pathological entity in the development of renal cysts. While there are limitations to the study of the cell outside of its tissue context, cellular measurements provide access to a number of sophisticated techniques to measure molecular function in living cells at high spatial and temporal resolution and can thus provide molecular evidence that ultimately can be verified within in vivo models. To build cellular level models of disease we require a wide variety of measurement modalities to relate specific genetic defects to a specific cellular phenotype. Many of the techniques used in this proposal can provide key molecular evidence for deficits in specific cellular pathways. The Imaging Core facility provides a unique and complementary set of microscopy-based modalities that can make high-resolution measurements of molecular function in living cells.